The composite hydrogel performs integrated PTT for osteogenesis and bacterial eradication. With NIR stimulation, precisely controlled-release of BMP-2 and tannin by the hydrophobic phenomenon of ...volume contraction along with local heating helps the osteogenic differentiation of BMSCs, and slow release of natural component O-HACC in combination with hyperthermia exhibits excellent antibacterial efficiency by relative low temperature to avoid potential unexpected damage.
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•A NIR-responsive and multi-functional hydrogel system packaged with bioactive factors was fabricated.•Programmable NIR irradiation performed anti-microbial, anti-oxidative and pro-osteogenic functions respectively.•Administration of controllable photothermal strategy achieved a synergistic therapeutic effect on bone regeneration.
Progress toward developing next-generation biomaterials applied in complex bone defect is expected to effectively integrate osteogenic and anti-bacteria capability. However, current biomaterials often achieve the two functions separately. Inspired by photothermal effect, exogenous light-induced thermal variations can efficiently facilitate bone regeneration and bacteria eradication. Here, a bioactive hydrogel BMP-2@PNH-TA with simultaneously osteogenic and anti-bacterial capacities is presented, which is based on the near infrared (NIR) induced photothermal effect to perform integrated photothermal therapy (PTT). In detail, photothermal effect and photothermal-controlled release of osteogenic and anti-bacterial factors through sponge-like effect could exert integrated influence on bone regeneration under complex situation. The composite hydrogel can mediate pro-osteogenesis under mild temperature and controlled release of BMP-2 and tannin in response to NIR stimulation with low power, while efficiently eradicate bacteria via controlled release of O-HACC and thermal effect with high power. The customized PTT strategy significantly shortened the duration time of bone regeneration up to almost 50% in rat cranial bone defect. It is anticipated that the concept of integrated PTT for bone regeneration will cast new insights into developing high-performance therapeutic strategy with combined biological functions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Recapitulating the natural extracellular physical microenvironment has emerged as a promising method for tissue regeneration, as multiple physical interventions, including ultrasound, thermal and ...electrical therapy, have shown great potential. However, simultaneous coupling of multiple physical cues to highly bio-mimick natural characteristics for improved tissue regeneration still remains formidable. Coupling of intrinsic electrical and mechanical cues has been regarded as an effective way to modulate tissue repair. Nevertheless, precise and convenient manipulation on coupling of mechano-electrical signals within extracellular environment to facilitate tissue regeneration remains challengeable. Herein, a photothermal-sensitive piezoelectric membrane was designed for simultaneous integration of electrical and mechanical signals in response to NIR irradiation. The high-performance mechano-electrical coupling under NIR exposure synergistically triggered the promotion of osteogenic differentiation of stem cells and enhances bone defect regeneration by increasing cellular mechanical sensing, attachment, spreading and cytoskeleton remodeling. This study highlights the coupling of mechanical signals and electrical cues for modulation of osteogenesis, and sheds light on alternative bone tissue engineering therapies with multiple integrated physical cues for tissue repair.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Mimicking the temporal pattern of biological behaviors during the natural repair process is a promising strategy for biomaterial-mediated tissue regeneration. However, precise regulation of dynamic ...cell behaviors allocated in a microenvironment post-implantation remains challenging until now. Here, remote tuning of electric cues is accomplished by wireless ultrasound stimulation (US) on an electroactive membrane for bone regeneration under a diabetic background. Programmable electric cues mediated by US from the piezoelectric membrane achieve the temporal regulation of macrophage polarization, satisfying the pattern of immunoregulation during the natural healing process and effectively promoting diabetic bone repair. Mechanistic insight reveals that the controllable decrease in AKT2 expression and phosphorylation could explain US-mediated macrophage polarization. This study exhibits a strategy aimed at precisely biosimulating the temporal regenerative pattern by controllable and programmable electric output for optimized diabetic tissue regeneration and provides basic insights into bionic design-based precision medicine achieved by intelligent and external field-responsive biomaterials.
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IJS, KILJ, NUK, PNG, UL, UM
The piezocatalytic nanocomposite membrane is fabricated by GO incorporation and PDA self-assembly. In response to external ultrasound exposure, high-performance electric output can be achieved. ...Composite membranes are implanted onto the surface of cranial bone defects, followed by ultrasound-mediated electric output for piezocatalytic therapy. In detail, piezoelectric output under ultrasound exposure triggers directional transport and emission of electron within built-in electric field, resulting in efficient recycling of redox activity from quinone group to phenolic group under diabetes-associated microenvironment full of oxidative products. This piezocatalytic strategy accomplishes persistent and long-term anti-oxidative potential for diabetic bone regeneration. Under the anti-oxidative treatment of piezocatalytic strategy, stagnated osteogenic differentiation of BMSCs and anti-inflammatory M2 macrophage polarization in hyperglycemic microenvironment have all been significantly promoted and enhanced, resulting in optimized diabetic bone repair.
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•Composite membranes exhibit excellent piezocatalytic potential.•Piezocatalytic effect performs efficient recycling of anti-oxidative reaction.•Piezocatalytic strategy executes high-performance ROS scavenging.•Piezocatalytic strategy significantly accelerates diabetic bone regeneration.
Anti-oxidative therapy for resistance of oxidative stress-induced damage has attracted substantial attention for bone regeneration under diabetic conditions. However, most anti-oxidants suffer from low efficiency due to their one-off reaction with oxidative products and rapid loss of activity. Herein, the piezoelectric nanocomposite with built-in electric field was fabricated as a cyclic anti-oxidative device for improved reactive oxygen species (ROS) scavenging and pro-osteogenic outcome. Under ultrasound (US) irradiation, the polydopamine (PDA) -functionalized generator with piezocatalytic effect exhibits high-performance recycling of redox catalytic reaction via continuous electron supplementation for cyclic group switch from quinone to phenol. The piezocatalytic method substantially boosts ROS elimination and reverses inflammatory status, contributing to strengthened osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and M2 polarization of macrophages. In vivo results further validated superior bone healing in rats with diabetes mellitus (DM). Our study therefore provides fundamental insights into the potential value of piezocatalytic effect-triggered cyclic anti-oxidative function for optimized osteogenesis under DM condition, and lays a basis for application of piezocatalytic effect in regenerative medicine.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Tumor-resident microbiota has been documented for various cancer types. Oral squamous cell carcinoma (OSCC) is also enriched with microbiota, while the significance of microbiota in shaping the OSCC ...microenvironment remains elusive.
We used bioinformatics and clinical sample analysis to explore relationship between F. nucleatum and OSCC progression. Xenograft tumor model, metabolic screening and RNA sequencing were performed to elucidate mechanisms of pro-tumor role of F. nucleatum.
We show that a major protumorigenic bacterium, F. nucleatum, accumulates in invasive margins of OSCC tissues and drives tumor-associated macrophages (TAMs) formation. The mechanistic dissection shows that OSCC-resident F. nucleatum triggers the GalNAc-Autophagy-TBC1D5 signaling, leading to GLUT1 aggregation in the plasma membrane and the deposition of extracellular lactate. Simultaneous functional inhibition of GalNAc and GLUT1 efficiently reduces TAMs formation and restrains OSCC progression.
These findings suggest that tumor-resident microbiota affects the immunomodulatory and protumorigenic microenvironment via modulating glycolysis and extracellular lactate deposition. The targeted intervention of this process could provide a distinct clinical strategy for patients with advanced OSCC.
This work was supported by the National Natural Science Foundation of China for Key Program Projects (82030070, to LC) and Distinguished Young Scholars (31725011, to LC), as well as Innovation Team Project of Hubei Province (2020CFA014, to LC).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Stem cell therapy serves as an effective treatment for bone regeneration. Nevertheless, stem cells from bone marrow and peripheral blood are still lacking homologous properties. Dental pulp stem ...cells (DPSCs) are derived from neural crest, in coincidence with maxillofacial tissues, thus attracting great interest in in situ maxillofacial regenerative medicine. However, insufficient number and heterogenous alteration of seed cells retard further exploration of DPSC‐based tissue engineering. Electric stimulation has recently attracted great interest in tissue regeneration. In this study, a novel DPSC‐loaded conductive hydrogel microspheres integrated with wireless electric generator is fabricated. Application of exogenous electric cues can promote stemness maintaining and heterogeneity suppression for unpredictable differentiation of encapsulated DPSCs. Further investigations observe that electric signal fine‐tunes regenerative niche by improvement on DPSC‐mediated paracrine pattern, evidenced by enhanced angiogenic behavior and upregulated anti‐inflammatory macrophage polarization. By wireless electric stimulation on implanted conductive hydrogel microspheres, loaded DPSCs facilitates the construction of immuno‐angiogenic niche at early stage of tissue repair, and further contributes to advanced autologous mandibular bone defect regeneration. This novel strategy of DPSC‐based tissue engineering exhibits promising translational and therapeutic potential for autologous maxillofacial tissue regeneration.
(A) Maxillofacial bone and teeth (yellow) are originated from an isogenic group of cells within neural crest. (B) Fabrication of conductive hydrogel microspheres. (C) DPSCs isolated form autologous teeth are encapsulated within hydrogel microspheres and injected into mandibular bone def. Nanogenerator is then subcutaneously implanted and connected to microspheres for electric output in response to ultrasound. (D) Improved paracrine behavior of DPSCs contributed to the construction of regenerative niche, resulting in facilitated mandibular bone regeneration.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background: Tumor-resident microbiota has been documented for various cancer types. Oral squamous cell carcinoma (OSCC) is also enriched with microbiota, while the significance of microbiota in ...shaping the OSCC microenvironment remains elusive. Methods: We used bioinformatics and clinical sample analysis to explore relationship between F. nucleatum and OSCC progression. Xenograft tumor model, metabolic screening and RNA sequencing were performed to elucidate mechanisms of pro-tumor role of F. nucleatum. Findings: We show that a major protumorigenic bacterium, F. nucleatum, accumulates in invasive margins of OSCC tissues and drives tumor-associated macrophages (TAMs) formation. The mechanistic dissection shows that OSCC-resident F. nucleatum triggers the GalNAc-Autophagy-TBC1D5 signaling, leading to GLUT1 aggregation in the plasma membrane and the deposition of extracellular lactate. Simultaneous functional inhibition of GalNAc and GLUT1 efficiently reduces TAMs formation and restrains OSCC progression. Interpretation: These findings suggest that tumor-resident microbiota affects the immunomodulatory and protumorigenic microenvironment via modulating glycolysis and extracellular lactate deposition. The targeted intervention of this process could provide a distinct clinical strategy for patients with advanced OSCC. Funding: This work was supported by the National Natural Science Foundation of China for Key Program Projects (82030070, to LC) and Distinguished Young Scholars (31725011, to LC), as well as Innovation Team Project of Hubei Province (2020CFA014, to LC).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
